The proposed research is based on the concept that particular DNA and RNA base sequences may directly control cellular functions by influencing secondary and tertiary polynucleotide conformations and that this gives the base sequence a fundamental importance in life processes over and above that due to the genetic code information which it may contain. There is ample evidence that secondary conformations of polynucleotides are dependent upon base sequence, and there is a growing body of knowledge which indicates that biological functions are directly controlled by simple sequences, such as poly r(A) stretches attached to messenger RNAs of mammalian cells, simple satellite DNA sequences interspersed within the genomes of higher organisms, the symmetrical sequences cleaved by restriction enzymes, and sequences such as poly r(I):r(C) which are potent inducers of interferon and can inhibit the multiplication of oncogenic viruses. However, confident interpretations of how such sequences exercise their biological functions await a complete understanding of the relationship between polynucleotide sequences and conformations; it is the goal of the proposed research to acquire an understanding of this key relationship. The research will utilize the sensitive technique of ultraviolet circular dichroism (CD) measurements to detect conformational differences among sets of selected synthetic DNA and RNA polymer sequences in solution. Then, influences of solvent conditions on these differences will be explored. The practicability of this approach has been demonstrated during the preceding grant period. The project will include acquiring a library of CD spectra which will be of great general utility for analyzing natural double-stranded DNAs for nearest-neighbor base frequencies and for characterizing the conformations of natural and synthetic DNAs, RNAs, and DNA:RNA hybrids in solution.